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Analysis of the interaction between mortality patterns and opportunity for natural selection could help to elucidate potential evolutionary implications of epidemic mortality. In this paper secular trends are studied in relation to Crow’s index (It) and its components of mortality (Im) and fertility (If ), using parish records for family reconstitution in a Basque population. A principal components analysis (91% of the variance accounted for) showed marked quantitative and qualitative variations of Im and If depending on the stage of demographic transition of the population analyzed: In pretransitional societies the opportunity for natural selection is determined mainly by differential prereproductive mortality, whereas in posttransitional societies selection resulting from differential fertility plays a key role. The highest values for the mortality component (range 0.81–1.26) and for the relative contribution of Im to It (range 47.1–57.2%) were observed in periods with a high incidence of infectious diseases and when the most severe mortality crises were detected (1830–1859, 1860–1889, and 1890–1919). A differential incidence of epidemic mortality was also found at prereproductive ages (before 16 years) and at reproductive ages (16–45 years), which provides strong support for the idea of the long-term genetic consequences of mortality crises.