OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral load within the first year (less or more than 1.5 x 10(4) copies/ml). RESULTS: High viral load at seroconversion was followed by a significant decline within the first months (P < 0.0005). Decline to < 1.5 x 10(4) copies/ml was correlated with slower progression to AIDS (P < 0.05). A correlation between the rate of CD4 decline and the median viral load during the ensuing viral load plateau phase was also shown (P < 0.05). Subsequent to this phase the viral burden increased. Rapid progressors had higher viral load than slow- or non-progressors; this was particularly pronounced late in infection. Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of seroconversion. A significant decline within the first months hereafter is followed by a plateau phase, which in turn is followed by an increase in HIV RNA. HIV RNA early in infection has a predictive value for the clinical outcome. The increased virulence of SI over NSI virus did not translate into significantly higher HIV RNA values.