Rioprostil is a synthetic prostaglandin E1 analogue currently under study for peptic ulcer healing. Rioprostil, like prostaglandin E, caused an impairment of glucose tolerance in animal studies. We have studied the effects of single therapeutic doses of rioprostil (300 micrograms and 600 micrograms) on glucose homeostasis after oral glucose tolerance tests in 12 healthy volunteers. Plasma glucose, insulin, and C-peptide concentrations were not significantly different after rioprostil and placebo. These results indicate that a clinically significant interference of rioprostil with glucose tolerance is unlikely.