We evaluated the treatment of asymptomatic patients with untreated syphilis of more than one year's duration (asymptomatic late syphilis) using a decision-analysis model. Two strategies were compared: treatment with 7.2 million units of penicillin G benzathine, or performing a lumbar puncture to test for asymptomatic neurosyphilis followed by penicillin and management based on cerebrospinal fluid analysis. Estimates of probabilities of disease prevalence, test sensitivity, and cure and complication rates were derived from published studies. Both strategies resulted in a cure rate of at least 99.7% using the best estimates. Although the strategy using lumbar puncture results in a 0.2% higher cure rate, its rate of complications (0.3%) exceeds its marginal benefit. We conclude that a lumbar puncture offers little additional benefit and may increase morbidity in patients with asymptomatic late syphilis.