This study has assessed the effect of oral or intraduodenal HC1, administered alone or in combination with glucose, on gastric inhibitory polypeptide (GIP) and insulin secretion. Eight young males were given the following three oral tests: 30 g glucose, 150 cc 0.1 N HC1 and the glucose-acid combination. Another group of eight controls received intraduodenal infusions of 20 g glucose, 75 cc 0.1 N HC1 and their combination. All tests were performed in a random fashion at weekly intervals. When given alone, HC1 did not influence glucose or insulin levels. However, HC1 did produce an increase in GIP. The GIP response to acid was less than that to glucose and was delayed. The peak insulin and GIP responses with the glucose and glucose/acid combinations were similar with both the oral and intraduodenal routes. There was, however, a potentiation of both the GIP and insulin responses when intraduodenal acid was given with glucose. This effect on GIP and insulin was not evident with the oral glucose/acid load. It is concluded that HC1 by itself is capable of stimulating GIP secretion. Since there was only a potentiation of insulin and GIP secretion when large doses of HC1 were given together with glucose via the intraduodenal route, the physiological relevance of acid-induced GIP secretion remains to be resolved.