The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.