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To determine the kinetics of decline of CD4+ lymphocytes in HIV-1-infected asymptomatic homosexual men.CD4 + lymphocytes were enumerated in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3-month intervals over 5 years. During follow-up, 45 men progressed to AIDS (excluding cases presenting with Kaposi's sarcoma). Correlation between rate of CD4+ cell decline and presence of a particular HIV-1 biological phenotype was analysed in 43 participants.CD4+ cell counts declined slowly and continuously in HIV-1-seropositive men who remained asymptomatic during follow-up. A biphasic CD4+ cell count decline was observed in the group who developed AIDS: the decline was slow and steady (5.6 × 106/1 per month, similar to that observed in the asymptomatic group) until 18 months before AIDS diagnosis, but became three to five times faster thereafter. Rapid CD4+ cell decline was significantly related to syncytium-inducing, fast-replicating HIV-1 isolates; during the period of slow and steady CD4+ cell count decline, non-syncytium-inducing isolates were predominant.At an average of 18 months preceding AIDS diagnosis, a three to fivefold increase in the rate of loss of CD4+ lymphocytes occurs, and may be related to the appearance of a more virulent HIV-1 phenotype.