Abstract This phase II pilot study investigated the once-daily activity of the calcium antagonist REC 15/2375 in the treatment of mild to moderate hypertension. Forty-nine patients were recruited for this double-blind, randomized trial, in which two dosing regimens of 10 mg or 20 mg once daily were administered for two treatment periods of 10 days each. Each patient completed a 14-day washout period and 7 days of a single-blind placebo run-in. The response after 10 days was evaluated. Sixty-four percent of the patients in the 20-mg group and 67% of the patients in the 10-mg group were classified as responders, that is, their diastolic blood pressure decreased to 90 mmHg or less. The responders continued with the same once-daily dosage, and the nonresponders continued with the same dosage given twice a day. On day 20 DBP was increased above 90 mmHg again in 3 of 16 responders in the 10-mg group; none of the responders in the 20-mg group worsened. No clinically relevant increase in heart rate was seen. REC 15/2375 was well tolerated in each dosage group. Our results indicate that REC 15/2375 might be effective in a once-daily regimen in the treatment of hypertension.