Tumor necrosis factor (TNF) is a pleiotropic cytokine with immunological and neuroendocrine activities. A useful tool for studying TNF is the measurement of its in vitro and/or ex vivo over-expression, induced by a variety of stimuli on isolated peripheral mononuclear cells or whole blood, respectively. The capacity to over-express TNF, in ex vivo LPS-stimulated whole blood from 18 normal individuals, showed inter-individual variations ranging from high (3 ng/ml) to low (0.7 ng/ml) producers. Although at a lower level, a similar situation was observed in the spontaneous production of the cytokine. In order to detect cyclic effects in these variations, blood samples were taken at 08:00, 12:00, 16:00 and 20:00 hours, from nine healthy volunteers, and cultured in the ex vivo system. TNF and cortisol were measured by immunometric assays. Both, LPS-stimulated whole blood and plasma showed important, individual variations in TNF levels. Although cortisol levels presented a normal circadian cycle, these individual patterns in TNF production were basically conserved during the day (p > 0.05), and no correlation was observed between the levels of the hormone and those of the cytokine. When total TNF levels were determined at 20:00 hours, a moderate, temporary variation pattern of the cytokine production was found. These results suggest that cortisol does not play a predominant role in determining the ex vivo capacity of blood to produce TNF. Presumably, the variable capacity to produce the cytokine may have a strong genetic component.