Prophylactic brain irradiation significantly reduces the proportion of patients with small cell carcinoma of the lung (SCCL) who develop brain metastases. Therapeutic brain irradiation could be used instead of prophylactic irradiation if it could be delivered promptly after diagnosis of intracranial spread and if it were highly effective. Forty of 188 patients with SCCL seen in the Medical College of Wisconsin Affiliated Hospitals had brain metastases either at initial diagnosis (23 patients) or after treatment (17 patients). Irradiation was administered to the whole brain at doses ranging from 3000 rads in 2 weeks to 4000 rads in 3 weeks. Neurologic function was the same for those patients with initial and delayed metastases and did not correlate with survival. Response to irradiation affected survival. After the diagnosis of brain metastases, survival was the same whether metastases were initially present or were delayed. Eighteen (45%) of the patients died from brain metastases and two (5%) are alive following disease recurrence in the brain. Increasing survival with SCCL due to effective chemotherapy is associated with an increasing failure rate in the brain which may eventually reach the 50% rate found at autopsy. Therapeutic brain irradiation is not sufficiently effective to preclude prophylactic irradiation.