The Publishing Room
Maintained by Raymond Long. Disclaimer: any information on this website could be wrong.
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Big publishing houses don't accept submissions directly from authors. They take submissions only through literary agents. Submitting to agents, you're entering a very competitive marketplace. I don't claim to know everything about it, but this is how that marketplace seems to me:

1. Big publishers, and therefore the agents who find them authors, are almost exclusively interested in books that fit well into an established genre. Before writing a book intended for an agent, study an existing target genre to write a book likely to get accepted. If you've written a book that doesn't fit into a well-known genre, you're better off submitting it directly to a small publisher.

2. Agents and big publishers don't want to take on a single novel. They want to take on an author who will keep writing books that sell well.

3. To keep writing books that sell well, an author needs to build up a fan base. These fans will want to read the same kind of book again and again. If you write a gritty New York murder mystery, people who liked it will want to read another gritty New York murder mystery by you, but most of them won't want to read a 17th century military adventure by you. Publishers favour authors who'll write a series of books with the same main characters and setting.

4. The first time you approach an agent, your submission should be finished and polished before you submit it. Agents generally don't want unrevised first drafts, and they don't want you to submit the start of a book if you haven't finished writing it.

Useful links: US agents and UK agents from The Writers' & Artists' Yearbook. Database of agents from firstwriter.com.

The agencies listed below appeared from their websites to be accepting submissions from new authors. Not all of them said this in so many words, but they seemed to be.

Agencies which accept submissions by email
John Jarrold (UK). www.johnjarrold.co.uk.
Wants: (2009-Aug) science fiction, fantasy and horror only
Eve White (UK). www.evewhite.co.uk.
Wants: (2009-Oct) literary and commercial fiction and non-fiction for adults, and children's fiction for 7+
Doesn't want: (2009-Oct) poetry, short stories or screenplays; science fiction and fantasy for adults
United Agents (UK). unitedagents.co.uk.

Agencies which accept submissions in hard copy (or I didn't see mention of how to submit)
Gregory & Co (UK). www.gregoryandcompany.co.uk.
Wants: (2009-Oct) new talent in the fields of excellent crime fiction, epic family sagas, historical and commercial novels and upmarket literary fiction
Doesn't want: (2009-Oct) children's books, science fiction and fantasy, chick-lit, poetry, short stories, plays/screenplays, spiritual or new-age philosophy, business
Ampersand (UK). www.theampersandagency.co.uk.
Wants: (2009-Oct) literary and commercial fiction and non-fiction, contemporary and historical novels, crime, thrillers, women’s fiction, memoirs, history, biography, cookery
Doesn't want: (2009-Oct) poetry, illustrated children’s books, fantasy, horror, science fiction, scripts
Artellus (UK, but accepts authors from across the world). www.artellusltd.co.uk.
Wants: (2009-Oct) new fiction writers, fantasy and science fiction, crime genres, as well as "literary"
Marjacq (UK). www.marjacq.com.
Wants: (2009-Oct) commercial and literary fiction and non-fiction; theatrical motion picture screenplays, TV and radio plays
Shiel Land (UK). www.sheilland.co.uk.
Inspira Group (UK). www.theinspiragroup.com.
Mic Cheetham (UK). www.miccheetham.com.
Claims: (2009-Oct) Takes on 2 or 3 new authors per year.