Actinomyces species are rare but treatable causes of CNS infection. Differentiation of actinomycosis from nocardiosis is crucial to the selection of appropriate antimicrobial therapy. A review of 70 cases of CNS actinomycosis was conducted in an effort to characterize clinicopathologic features and identify patients with a high risk of death from infection. Types of lesions included brain abscess (67%), meningitis or meningoencephalitis (13%), actinomycoma (7%), subdural empyema (6%), and epidural abscess (6%). Most infections developed from distant sites (lung, 19 cases; abdomen, four; pelvis, three) or contiguous foci (ear, sinus, and cervicofacial region, 21 cases). For nonmeningitic infection, signs and symptoms were generally those of a space-occupying lesion and were indistinguishable from the manifestations of other pyogenic infections except for a longer interval before diagnosis. Risk factors included dental caries; dental infection; recent tooth extraction; head trauma; gastrointestinal tract surgery; chronic otitis, mastoiditis, or sinusitis; chronic osteomyelitis; tetralogy of Fallot; and actinomyces infection of an intrauterine device. Optimal management combined adequate surgical drainage with prolonged antibiotic therapy (mean duration, 5 months). Overall mortality from treated infection was 28%; 54% of survivors had neurologic sequelae. Features correlated with a poor prognosis were disease onset greater than 2 months before diagnosis and treatment, no antibiotic treatment, no surgery, and needle aspiration drainage of abscess lesions.