Animal models were designed to study the changes in immune function, oncogenicity and life span of rats, mice and fruit flies following light-dark (LD) shift manipulations. Alternating the photoperiod of LD 14:10 and DL 10:14 every 3 days in rats disrupted the circadian immune rhythm pattern, decreased the blood leukocyte concentration by 48% and lowered the percentage of lymphocytes in the blood from 71% (control) to 49.2%. In mice, the phagocytosis of neutrophils was only reduced by 7%, but the level of serum hemolysin dropped significantly in the photoperiod-shifted group as compared with animals kept under a constant photoperiod of LD 12:12 or LD 14:10. In Ehrlich-carcinoma- or sarcoma-180-injected mice, a reduction of survival duration, acceleration of tumor growth and depression of the immune system were recorded in the LD-shifted animals. In addition, the life span of fruit flies was shortened by 9.6% by photoperiodic shifting. Melatonin treatment evidently counteracted the deleterious influences of photoperiodic shifting in the above animals. It is suggested that repeated inversion of the LD cycle results in a chronobiological abnormality that, in turn, induces dysfunctions. Reentrainment by exogenous melatonin may inhibit the harmful influences of photoperiodic shifting.