Controversial aspects relating to acid secretory changes following duodenal ulcer healing, and the effect of histamine-2 (H2)-receptor blockers on such changes are discussed. Recent studies comparing the effects of ranitidine or sucralfate on changes in the acid secretory responses in the healing of duodenal ulcers are described, and the relevance of these changes to early relapse considered. The duration of therapy and timing of acid-secretory studies and endoscopies are standardized in all studies, but the acid-secretory parameters vary. These comprised acid secretory responses to graded doses of an intravenous infusion of pentagastrin or histamine, sham-feeding responses, and basal and nocturnal acid secretion. In all studies, healing with sucralfate was associated with a significant decrease in the various parameters of acid secretion. In the ranitidine-healed groups, no appreciable decrease was noted and there was, indeed, a significant increase in nocturnal acid secretion. Routine endoscopies performed 4-6 weeks after documented ulcer healing showed a recurrence of 3 of the 32 (9%) sucralfate-healed and in 14 of the 35 (40%) ranitidine-healed ulcers. Increased acid secretory responsiveness following duodenal ulcer healing was strongly correlated with subsequent early relapse.