Recently evidence has been provided for a genetic control of T-cell dependent cytokine production by HLA-class II. Candidate genes in multiple sclerosis, a T-cell mediated autoimmune disease, are the disease-associated DR2, DQ6, Dw2 haplotype. Previous observations by us and others imply a HLA-DR2 dependent propensity of antigen-specific T-cell lines to produce increased amounts of TNF-alpha/beta. Here, we tested a possible association between HLA or disease status with cytokine production employing the simple and widely used method of bulk cultures. Peripheral blood cells of 48 patients and 68 healthy individuals were analyzed. We observed no significant differences of the cytokine production in relation to disease status or any HLA polymorphism. Our data indicate that, in contrast to monoclonal T-cell cultures, bulk cultures are not suitable to detect immunogenetic control of T-cell function.