We studied the natural history and response to treatment in 50 patients with splenic lymphoma with villous lymphocytes followed for a minimum of 6 months and up to 15 years (median 3.7 years). The disease occurs in the elderly (median 68 years) and affects males more than females (M/F ratio 1.77). The median survival for the group was not reached but 82% were surviving at 3 years and 78% at 5 years. Twelve patients (24%) died, one-third of deaths were disease related (four patients) and one-half were due to cardiovascular disease or another malignancy (six patients). The outcome was worse for males (31% died) than females (11% died). Fourteen patients were not treated and 10 remain alive between 1 and 6 years from diagnosis. The remaining patients were treated by chemotherapy, splenic irradiation or splenectomy. The response to chemotherapy was poor and only eight of 22 (36%) patients treated achieved a good response. Splenic irradiation was employed in seven patients and three benefited from it. Splenectomy seems to be the treatment of choice, with significant improvement seen in 19 of 20 patients with one post-operative death. This response, lasting from 6 months to 7 years (median 4 years), was seen irrespective of whether splenectomy was the initial treatment or used later in management.