To compare the efficacy and side effects of two xanthine derivatives in the maintenance therapy of reversible obstructive airway disease, 242 patients were assigned in randomized, double-blind fashion to receive either oral enprofylline or theophylline for 5 weeks in addition to their usual maintenance regimens. After a week of placebo xanthine therapy, enprofylline-treated patients received 150 mg of this drug twice daily (b.i.d.) for 3 days, 300 mg b.i.d. for 2 weeks, and 450 mg b.i.d. for 2 weeks. Theophylline was administered in identical doses, except that the final dosage increase was not made if plasma theophylline was 12 mg/ml or higher. At 300 mg b.i.d., both drugs significantly increased morning peak expiratory flow rate (PEFR), the mean increase above baseline being significantly higher for theophylline-treated patients (29.9 +/- 37.2 L/min) than for enprofylline-treated patients (17.4 +/- 36.9 L/min) (p = 0.023). At 450 mg b.i.d., improvement in morning PEFR was not significantly different between theophylline-treated (31.5 +/- 44.4 L/min) and enprofylline-treated groups (23.5 +/- 48.4 L/min). Evening PEFR, FEV1, and asthma symptom scores also improved significantly, demonstrating no significant difference between groups. The incidence of side effects was also similar between groups. We conclude that both enprofylline and theophylline offer useful bronchodilatation in the maintenance therapy of asthma, enprofylline, 450 mg b.i.d., being approximately equivalent to theophylline, 300 or 450 mg b.i.d.