OBJECTIVE: To investigate the effect of pregnancy on HIV disease progression and survival among HIV-infected women in rural Uganda, prior to the introduction of anti-retroviral therapy (ART). METHODS: From a clinical cohort established in 1990, we selected records from HIV-infected women of reproductive age. We conducted two analyses: (1) all HIV-infected cases contributing to analysis of CD4 decline, using a linear regression model with random intercepts and slopes; (b) incident cases with known date of seroconversion contributed to analyses of median time to CD4 <200 cells/microl, AIDS and death. RESULTS: A total of 139 women were included in the analysis of CD4 decline. Women who subsequently became pregnant had higher CD4 counts at enrolment and had a slower CD4 decline than those who did not become pregnant. In women who became pregnant, CD4 decline was faster after pregnancy than before (P < 0.0001). The survival analyses showed no significant differences between women who became pregnant and those who did not with respect to median time to CD4 count <200, AIDS or death. CONCLUSIONS: The initial comparative immunological advantage possessed by fertile women before they become pregnant is subsequently lost as a result of their pregnancy. Women should be informed about the potential negative effect of pregnancy on their immunological status and should be offered contraception. In resource-limited settings, women determined to become pregnant should be given priority for ART if eligible.