A case is described of a patient with Bactrim-induced fixed drug eruption (FDE). Histological studies were performed at 1 day and 5 days after the drug exposure. While the 5-day-old lesion showed changes classically recognized as FDE, the 1-day-old lesion showed changes typical of a hypersensitivity response: diffuse spongiosis, dermal edema and hemorrhage, neutrophilic polymorphonuclear leukocyte abscess formations, and large numbers of eosinophils. This report underscores the dynamic cellular changes that occur in the evolving FDE lesion.