Antigenic properties of the V3 region are reflected by HIV-1 serotypes. These may represent biological properties of the virus. We serotyped HIV-1 in 142 serum samples from participants in a rural Uganda cohort who seroconverted between August 1991 and December 2001. Clinical progression was assessed using Cox proportional hazards and Kaplan-Meier methods. Of 112 (79%) samples successfully serotyped, 36% were serotype A, 17% serotype B, 18% serotype C, and 29% serotype D. Median follow-up time, age at enrollment, and first CD4 count were similar in each serotype group. Clinical progression was faster for serotype D than other serotypes to AIDS or death, death, and CD4 count <200 cells/mm(3) (all p < 0.05). HIV-1 V3 serotypes are associated with variations in the pathogenicity of HIV-1 and should be taken into account when studying the biological relevance of HIV-1 diversity.