The effects of theophylline on T-lymphocyte colony formation were investigated both by in vitro studies (adding theophylline in cultures at three different concentrations--5, 15 and 30 micrograms/ml) and by in vivo experiments (after oral ingestion of 10 mg/kg time-released theophylline) in a group of young healthy volunteers. In vitro the drug showed a significant dose-dependent inhibitory effect on both peripheral mononuclear cells (PMNC) and purified T-lymphocyte colony formation. No significant differences in PMNC colony formation before and 12 h after the oral ingestion of theophylline was detected in the in vivo study, even if at the same time the plasma concentration of the drug remained at therapeutic level in every subject. In addition, in vitro experiments mimicking the in vivo conditions suggested that the apparent disagreement between the in vitro and in vivo results was due to experimental procedures (i.e. the inhibitory effect requires the constant presence of the theophylline in the culture medium). The experimental data provided in this study confirm, using different experimental procedures, the results of our recent investigations showing that theophylline exerts an inhibitory effect on T-cell proliferation.