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The study investigated whether clients of sex workers are a bridge for transmission of HIV to the general population of Cambodia. We interviewed and collected blood from 468 clients attending 30 randomly selected brothels in three provinces of Cambodia. The levels of HIV knowledge and condom use, and prevalence of HIV (9.2%) were high. Almost 40% of those interviewed had sex with women other than sex workers (wives, girlfriends, etc.), but rarely used condoms. Sexually transmitted disease (STD) rates were high, but most sought treatment from pharmacies. HIV infection was correlated with a history of STD, having had an HIV test, not living with one's wife, a high level of HIV/AIDS knowledge, and condom slippage/breakage. Clients are a major bridge for HIV transmission from sex workers. Current condom promotion programmes need to target non-sex worker intercourse. More effective, acceptable STD-control strategies need to be implemented and evaluated.