To identify determinants of HIV seroconversion among injection drug users (IDUs) during a period of rising prevalence, a case-control investigation was conducted. Cases were IDUs with a new positive test after 1 January 1994, and a negative test within the prior 18 months. Controls required 2 negative tests during the same period. Subjects completed a questionnaire on demographic, psychosocial, and behavioural factors. Eighty-nine cases and 192 controls were similar with respect to gender, age, ethnicity and inter-test interval. Multivariate analyses of events during the inter-test interval showed borrowing syringes (adj. OR = 2.96; P < 0.006), unstable housing (adj. OR = 2.01; P = 0.03) and injecting > or = 4 times daily (adj. OR = 1.71; P = 0.06) to be independently associated with seroconversion. Protective associations were demonstrated for sex with opposite gender (adj. OR = 0.36; P = 0.001) and tetrahydrocannabinol use (adj. OR = 0.41; P = 0.001). There is a need to evaluate programmes dealing with addiction, housing and the social underpinnings of risk behaviours in this population.