The in vivo effect of theophylline on lymphocyte nucleotide metabolism was investigated. Rat peripheral blood lymphocytes presented more elevated levels of adenosine 5'-triphosphate (ATP) and cyclic adenosine 3',5'-monophosphate (cAMP) than shown by spleen lymphocytes. A continuous (15 days) daily oral treatment of the rats with aminophylline increased intralymphocytic cAMp content in peripheral blood (by 14 times) and in spleen lymphocytes (by 4 times), whereas ATP content was not significantly changed. NAD+ and NADH levels and NAD+/NADH ratios appeared higher in peripheral blood than in spleen cells, and were not influenced by aminophylline treatment. These results may be explained by assuming the existence of a different distribution of lymphocyte subpopulations and of a different sensitivity of the same to aminophylline treatment. The studies of nucleotide variation in peripheral blood lymphocytes incubated at 37 degrees C in anoxic conditions (N2+CO2, 95:5) revealed an impairment of ATP production and a well-preserved redox state.