Recent evidence suggests that as a group protease inhibitors (PIs) may accelerate certain factors associated with atherosclerosis. The objective of this study was to evaluate the effect of individual PIs (indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) on certain factors associated with atherosclerosis. Persons who took saquinavir and/or ritonavir were compared with those on other PIs. Between May 2000 and July 2001, the lipid profiles, C-reactive protein (CRP) levels, coronary artery calcium (CAC) scores, and blood cell morphologic parameters were measured in 98 black adult participants aged 25 to 45 years with HIV-1 infection in Baltimore, Maryland. Among these 98, there were 55 (56.1%) taking PIs. Students' t-test and chi2 test were used to detect the between-group differences. Study participants in both the PI and non-PI groups were similar in age, sex, body mass index, blood pressure, red and white blood cell counts, time since HIV diagnosis, and duration on anti-retroviral therapy. Compared with those who took non-PI regimens, those who took indinavir, nelfinavir, or saquinavir had significantly higher levels of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Those taking any PI had significantly higher total cholesterol and low-density lipoprotein. Those taking nelfinavir, ritonavir, or saquinavir were more likely to have a higher CAC score (>5) than those on non-PI regimens. There were no differences in the lipid profiles, MCV, MCH, CRP, and CAC between those taking saquinavir and/or ritonavir and those taking other PIs. Overall, the changes noted might lead to anticipation of clinical changes linked to accelerated atherosclerosis in patients on PIs.