Adherence to prescribed medications is a central feature of good clinical HIV care, but little is known about the factors associated with multidrug antiretroviral adherence, or about how such adherence is related to plasma HIV suppression. We collected data from 133 HIV-infected adults receiving antiretroviral therapy. Study subjects completed customized adherence self-report instruments and provided blood samples to measure plasma HIV-1 RNA concentrations and CD4+ lymphocyte counts. Regression models were used to determine the independent predictors of antiretroviral adherence and plasma HIV concentration, and the relationships between the two. Adherence was poor (average, <80% antiretrovirals/day) in 28% (95% confidence interval [CI], 20%-36%), fair (80%-99% per day) in 23% (95% CI, 15%-30%), and excellent (100% per day) in 50% (95% CI, 41%-58%) of study subjects. Mean decreases in HIV-1 concentration from highest-ever levels were 1.3, 1.6, and 2.0 log10 copies/ml in these three groups, respectively (chi2; p < .02). Two-stage least squares regression demonstrated a -1.3 log difference in viral load associated with each category improvement in adherence. In multivariate models, confidence in medication-taking ability, or perceived self-efficacy, and convenience of the medication regimen, or "fit" with routine and daily activities, were also associated with greater medication adherence (odds ratios [OR] 5.3; 95% CI, 2.4-11.8, and 9.0; 95% CI, 1.8-45.3, respectively). The latter was also independently associated with a lower plasma HIV concentration (p < .02). Nonadherence to combination antiretroviral medications is common and is associated with increased levels of plasma HIV. Programs and clinical efforts to improve medication taking should strive to integrate medications better into patients' daily routines and to improve patients' confidence in their ability to take medications correctly.