Lesions of erythema multiforeme from seventy-five patients have been studied histologically. In addition to peculiar intercellular epidermal oedema, subepidermal separation and a lymphohistiocytic inflammatory infiltrate in the papillary dermis, epidermal cell necrosis was observed in a variable percentage of the lesions. While dermal disturbance was a predominant finding in the macular lesions, focal or generalized keratinocytic necrosis was seen in the macular, papular, bullous and iris lesions in that order of frequency. Significant numbers of eosinophils were present in the inflammatory infiltrate in 60% of the bullous and 28% of the macular lesions. Our findings suggest that erythema nultiforme represents a tissue reaction with spectral expression, one end presenting as a predominantly dermal disturbance and the other merging into the adult type of toxic epidermal necrolysis. Yet, the histological features remain sufficiently characteristic for differentiation from other erythematous and vesiculobullous eruptions.