Background: The seasonal variation of peptic ulcers is a rhythmic phenomenon reported worldwide, exhibiting diverse patterns and controversies. Unfortunately, it has remained an unresolved mystery for more than 90 years. Numerous studies have found that this phenomenon was closely associated with multiple environmental factors, but the underlying mechanism has never been elucidated. Objectives: This study aims to elucidate the seasonal variation of peptic ulcers and identify the role of environmental factors in the disease. Methods: Based on a recently identified etiology of peptic ulcers, two inverse operations in calculus, differentiation and integration, are iterated to analyze the existing data. First, the fluctuation curve in the seasonal variation is differentiated twice into the monthly incidences caused by multiple individual environmental factors, and the fluctuation curve due to each individual environmental factor is generated separately. Second, the monthly incidences caused by the individual environmental factors are integrated twice to reproduce the fluctuation curves in the seasonal variation of peptic ulcers. Results: The differentiations of the fluctuation curves in the season variation reveal a parallel relationship between the psychological impacts of each individual environmental factor and the monthly incidences of peptic ulcers. The integrations of the monthly incidences caused by 3 environmental factors reproduce the fluctuation curves in 3 representative seasonal patterns of peptic ulcers but make the parallel relationships invisible. Discussion: The parallel relationships revealed a causal role of environmental factors in peptic ulcers, whereas the reproduction of the fluctuation curves elucidated that multiple environmental factors cause the seasonal variation of peptic ulcers by Superposition Mechanism. The regional differences in environmental factors result in the diverse patterns, as well as the controversy questioning the seasonality of peptic ulcers. Significantly, the data analyses exemplify the application of a new concept, Superposition Mechanism, which might be an indispensable methodological complement to life science and medicine.