Lymphocyte subpopulations present circadian variation of some of their subsets, this variation may influence magnitude and expression of the immune responses and may be related to the variation of neuro-endocrine humoral factors. In our study cortisol, melatonin, TRH, TSH, FT4, GH, IGF1 and IL2 serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from 11 healthy male subjects aged 38-55 years. A clear circadian rhythm was validated for cortisol serum levels, CD8, CD16, TcRδ1 with acrophase in the morning and at noon, and for melatonin, TRH, TSH, GH, CD3, CD4, CD4/CD8 ratio, HLA-DR, CD20 and CD25 with acrophase at night. Changes of serum levels of FT4, IGF1 and IL2 did not show circadian rhythmicity. In the photoperiod (06.00-18.00h) and in the scotoperiod (18.00-06.00h) there were significant correlations among the lymphocyte subpopulations and humoral factors studied. The results show that specific lymphocyte subsets present different profiles of nyctohemeral changes and different timed relationships with neuro-endocrine hormones.