Objective: To determine the safety and pharmacokinetics of the nucleoside analogue, 3TC. Design: A Phase I, open-label, single-centre study. Methods: Twenty asymptomatic, HIV-infected male patients with CD4 lymphocyte counts <500 x 106/l who had not received previous antiretroviral therapy completed the study. Each patient received a single intravenous dose followed by a single oral dose of 3TC. Four patients were dosed at each of five dose levels (0.25,1.0, 2.0, 4.0 and 8.0 mg/kg). Results: The most commonly reported adverse event was headache, which was generally reported to be mild. The mean bioavailability of 3TC was 82% following oral administration. The majority of the dose (approximately 70%) was excreted unchanged in the urine. Conclusions: Overall, 3TC was well tolerated following dosing, and there were no significant changes in the safety parameters measured. Phase I/II clinical trials with 3TC are ongoing to evaluate its safety, pharmacokinetics and preliminary activity.