A cross-sectional study of 132 adults attending an HIV clinic in Cape Town, South Africa, was conducted to determine predictors of low plasma vitamin A and Zn levels. No patients were on antiretroviral therapy. The possible confounding effect of the acute-phase response was controlled by including C-reactive protein levels in multivariate analysis and by excluding active opportunistic infections. Retinol levels were low (<1.05 micromol/l) in 39 % of patients with early disease (WHO clinical stages I and II) compared with 48 and 79 % of patients with WHO stage III and IV respectively (P<0.01). Plasma Zn levels were low (<10.7 micromol/l) in 20 % of patients with early disease v. 36 and 45 % with stage III and IV disease respectively (P<0.05). C-reactive protein levels were normal in 63 % of subjects. Weak, positive associations were found between CD4+ lymphocyte count and plasma levels of retinol (r 0.27; 95 % CI 0.1, 0.43) and Zn (r 0.31; 95 % CI 0.25, 0.46). Multivariate analysis showed the following independent predictors of low retinol levels: WHO stage IV (odds ratio 3.4; 95 % CI 2.1, 5.7) and body weight (odds ratio per 5 kg decrease 1.15; 95 % CI, 1.08, 1.25), while only body weight was significantly associated with low Zn levels (OR per 5 kg decrease 1.19; 95 % CI 1.09, 1.30). CD4+ lymphocyte count <200/microl was not significantly associated with either low retinol or Zn levels. In resource-poor settings, simple clinical features (advanced disease and/or weight loss) are associated with lowered blood concentrations of vitamin A and/or Zn. The clinical significance of low plasma retinol and/or Zn levels is unclear and more research is required to establish the role of multiple micronutrient intervention strategies in HIV disease.