Lactic acidosis is a serious complication of antiretroviral therapy. Symptomatic hyperlactataemia is a milder form of this syndrome, but its incidence is unclear. In this prospective ongoing observational study of a large cohort of HIV-infected adults, hyperlactataemia was diagnosed in 64 patients. Incidences were 18.3/1000 person-years with antiretroviral therapy, and 35.8/1000 person-years for stavudine (d4T) regimens. Ten of the 64 patients developed lactic acidosis during the first 13 months of treatment (incidence 2.9/1000 treated person-years). In four of ten patients, symptoms were absent or mild. More patients on d4T first-line therapy developed lactic acidosis than patients previously treated with other drugs (p = 0.008). Despite the occurrence of one death, the subsequent outcome for the remaining patients was favourable after antiretroviral therapy was stopped and supportive treatment with vitamins and antioxidants initiated. The early diagnosis of cases was the result of great vigilance and, combined with routine measurements of the anion gap, might be the most crucial factor explaining the low mortality rate observed here.