The factors predisposing to an aggressive clinical course in cavernous malformations of the brain are not known. Disabilities from neurological deficits and from seizures were assessed and graded in 84 patients harboring 100 cavernous malformations and were correlated with patient sex and age, lesion size, lesion location, lesion multiplicity, and previous overt hemorrhage. Univariate analysis showed that female sex, infratentorial lesion location, and previous gross hemorrhage were significantly associated with subsequent neurological disability. Logistic regression analysis showed that infratentorial lesion location and previous gross hemorrhage were independent factors simultaneously and significantly associated with neurological disability. Age less than 40 was the only significant factor predisposing to seizure disability (in both univariate and multivariate analyses). Lesion size, multiplicity, and other factors did not influence clinical disability. This information should assist in management decisions regarding cavernous malformations.