Reliable data on the incidence and severity of nausea accompanying combination antiretroviral therapies is lacking. A prospective time series design was used to assess the rate, severity, and distress of nausea in a cohort of 75 HIV-positive patients who were beginning or changing a combination of two or more antiretroviral medications. Data were collected via telephone at weekly intervals for 12 weeks. The rate of nausea across regimens was greatest at Week 1 (39%) and declined progressively over time. By Week 12, the rate of nausea was only 5%. Severity of nausea was ranked as moderate or severe by a substantial proportion of patients through Week 10; however, nausea severity and distress were also found to diminish over time. The nausea associated with combination antiretroviral therapy is quite common and may adversely affect medication adherence. Findings indicate that clinicians should consider initiating interventions for management of antiretroviral-related nausea at baseline.