Cross-sectional analysis of 252 paired serum and peripheral blood mononuclear cell (PBMC) samples derived from 54 human immunodeficiency virus type 1 (HIV-1)-infected persons revealed a correlation between HIV-1 RNA load in serum and infectious load in peripheral CD4 T cells after 18 months of follow-up and before an AIDS diagnosis (Pearson's correlation coefficient [r(p)] = .71, P < .001) and during antiviral treatment (r[p] = .78, P < .001). To gain insight into the temporal relationship between both measures of virus load, longitudinally obtained samples from 23 persons with various clinical courses (slow or rapid disease progression, long-term survival) and 22 persons undergoing antiviral therapy (zidovudine or didanosine, or both, or ritonavir) were analyzed. In general, the kinetics of changes in both measures of virus load were similar in the natural course of infection (78% of study participants) and during treatment (82% of participants). These findings suggest that PBMC and serum represent closely related, if not the same, viral compartments.