We investigated the effect of aminophylline on the pituitary-thyroid axis in 13 asthmatics (21-71 yr). Aminophylline (250 mg), dissolved in 100 ml of saline, was given intravenously for 30 min. Blood was collected, before and 30, 60 and 120 min after beginning the injection. Serum TSH was significantly increased from the 2.2 +/- 1.6 microU/ml baseline to 2.7 +/- 1.9 microU/ml at 60 min (p less than 0.01), and to 2.8 +/- 2.1 microU/ml at 120 min (p less than 0.05). Serum T4 also rose from the 8.8 +/- 1.2 micrograms/dl baseline to 9.6 +/- 1.5 micrograms/dl at 120 min (p less than 0.05). There were no changes in serum T3 and rT3 levels. Correlations between increase of theophylline and TSH levels, and between increases in TSH and T4 concentrations, were observed. Since aminophylline stimulates the secretions of catecholamine from the sympathetic nerve endings and the adrenal medulla, we assumed that TRH was released from the hypothalamus by a beta-2-receptor mechanism because TSH secretion had been stimulated. These findings suggested that aminophylline-induced T4 release from the thyroid is mediated by released TSH and by the direct stimulatory effects of raised endogenous catecholamine on the thyroid.