In the field of diagnostic reasoning, it has been argued that memory activation can provide the reasoner with a subset of possible explanations from memory that are highly adaptive for the task at hand. However, few studies have experimentally tested this assumption. Even less empirical and theoretical work has investigated how newly incoming observations affect the availability of explanations in memory over time. In this article we present the results of 2 experiments in which we address these questions. While participants diagnosed sequentially presented medical symptoms, the availability of potential explanations in memory was measured with an implicit probe reaction time task. The results of the experiments were used to test 4 quantitative cognitive models. The models share the general assumption that observations can activate and inhibit explanations in memory. They vary with respect to how newly incoming observations affect the availability of explanations over time. The data of both experiments were predicted best by a model in which all observations in working memory have the same potential to activate explanations from long-term memory and in which these observations do not decay. The results illustrate the power of memory activation processes and show where additional deliberate reasoning strategies might come into play.