Reverse transcriptase has been detected in the serum of HIV-negative patients with amyotrophic lateral sclerosis (ALS). An ALS-like disorder in HIV-positive patients can remit with antiretroviral therapy. Using the product enhanced assay technique, we measured reverse transcriptase activity in the serum and CSF of 23 HIV-negative patients with ALS and 21 neurologic disease controls. Results for CSF were not significant, whereas reverse transcriptase was detected in 56% of ALS sera vs 19% of controls.