Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA in 4.5-h, lipopolysaccharide-stimulated whole blood cultures of 347 human immunodeficiency virus type 1-infected patients and 107 healthy seronegative controls. The production of TNF-α was decreased in both AIDS and non-AIDS patients, whereas the production of IL-1β was decreased in AIDS patients only. The production of TNF-α and IL-1β was positively affected by the concentrations of CD14+ monocytes and CD8+ lymphocytes; however, in patients, the concentration of CD4+ lymphocytes and the presence of AIDS had a negative effect on cytokine production as determined by multiple linear regression analysis. It is concluded that low whole blood cytokine production is mainly caused by low numbers of cells, but a functional defect may also exist.