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The case histories of two patients with clinically diverse forms of the very rare entity primary, spontaneous mesencephalic hemorrhage are presented. Each exhibited characteristic mesencephalic signs and neuroimaging profiles. However, both patients differed markedly in their predisposing factors, state of arousal, memory, temporal course and functional residua. One patient was unique in displaying a normal level of alertness throughout his clinical course and an isolated retrograde amnesia. The latter sign suggests a role for mesencephalic reticular activation in long-term retrieval and illustrates the differential effects of a subtle activation deficit on memory and arousal. These findings broaden the distinctive clinico-anatomical profile of primary, spontaneous mesencephalic hemorrhage.