In order to establish whether the age-related reduced growth hormone (GH) responsiveness to GH-releasing hormone (GHRH) could be improved by treatment with low amounts of theophylline, a drug mainly acting through cyclic adenosine 3', 5'-monophosphate (cAMP), and calcium-mediated mechanisms, eight adult subjects (aged 20-37) and eight elderly men (aged 64-79) were tested with GHRH (50 micrograms in an iv bolus), theophylline (1.67 mg/min for 3 h), or the combination of both drugs. The GH response to GHRH was significantly lower in the older than in the younger group (mean peaks were 4.5 and 7.5 times higher than baseline, respectively). Theophylline did not change basal GH levels in any subjects and GHRH-induced GH rise in the younger group, whereas it restored normal GH responses to GHRH in the older subjects (mean peak responses were eight times higher than baseline in both groups). These data show that in elderly subjects the mechanism underlying the GHRH-induced GH secretion may be fully activated by GHRH during treatment with low amounts of theophylline.