Stavudine, 2',3'-didehydro-3'-deoxythymidine (D4T), is a potent inhibitor of HIV-1 reverse transcriptase in vitro. In clinical studies, stavudine has excellent oral bioavailability in excess of 80%. The dose-limiting toxicity is peripheral neuropathy, which occurred in 15% of stavudine versus 6% of zidovudine-treated patients for 80 weeks in a randomized, blinded, phase III trial. Stavudine-treated groups have experienced significant increases in mean CD4 cell counts and decreases in both mean serum p24 antigen levels and infectious HIV titers in peripheral blood mononuclear cells. In subjects with prior zidovudine treatment, the duration of these responses is limited; CD4 counts and serum p24 antigen levels return to baseline after approximately 6 months. The effect of stavudine on clinical outcome and survival has not yet been established in comparative trials. Stavudine offers an additional therapeutic option to those individuals who are refractory to or intolerant of other available antiretrovirals.