This study compared the results of two analytic methods testing the effects of histamine H2 receptor antagonists on acid-related conditions. We examined the rates of peptic ulcer disease-related and of gastritis- and duodenitis-related mortality, hospitalizations, surgery, physician visits, work-loss, and disability retirements in the United States from 1970 to 1986. First, we performed a nonparametric epidemiologic analysis. For mortality, hospitalizations, and surgeries, age-specific rates continued their historic decline; there was an additional large one-time decline of operations in 1978. Trends were stronger for peptic ulcer than for gastritis and duodenitis. From pooled annual data, rates of physician visits and physician referral declined for peptic ulcer and for gastritis and duodenitis in the post-1977 period (p = 0.0001). Work-loss and other restrictions on normal daily activities also declined for persons with peptic ulcer and with gastritis and duodenitis (p = 0.0001). Second, we fit a parametric model by maximum likelihood to test specific population effects of H2 blockers. The model indicated that people >65 years old had increasing peptic ulcer mortality rates after 1977 (p < 0.001), while people < 65 years old had a deceleration in rates of decline (p < 0.01). Hospitalization rates for peptic ulcer and for gastritis and duodenitis increased in the elderly after 1977 (p < 0.01) and decreased among those < 65 years old. Both age groups experienced similar declining trends of operations for peptic ulcer; these were not significantly different when pre- and post-1977 periods were compared. The rate of disability retirement declined sharply for workers >50 years old (p < 0.01) and for those < 50 years of age (p < 0.001). The inconclusive results of the parametric analysis, plus only partial congruence between parametric and nonparametric analyses, emphasize the difficulty of relating diverse effects over time to a single, new, more effective treatment.