The effect of ketanserin on intermittent claudication was assessed in 13 placebo-controlled parallel group studies following basically the same protocol. After a single-blind placebo run-in period of 1-2 months, the patients randomly received either ketanserin (n = 152) or placebo (n = 158) for 3-6 months. Data on walking distance, assessed on the treadmill, were available in 12 centers (239 patients). Walking distance significantly increased in seven centers with ketanserin and in two centers with placebo. In two centers, the intergroup comparison between ketanserin and placebo was significantly in favor of ketanserin; in one center, it was in favor of placebo. A pooled analysis of all data on walking distance showed that ketanserin significantly increased walking distance by 65%, whereas placebo significantly increased it by 25%. However, the intergroup comparison does not show significant differences. Comparison of individual responses, on the other hand, showed that more patients experienced a doubling of walking distance on ketanserin than on placebo (25 versus 13%), and fewer patients deteriorated on ketanserin than on placebo (23 versus 32%); this difference in response rate is significant (p less than 0.05). In these studies there was a striking difference in drop-out rate between ketanserin and placebo. In total, 25 patients dropped out during placebo treatment versus 14 during ketanserin treatment. Nine of the 25 dropouts on placebo suffered severe "cardiovascular events," whereas no such events were observed in the ketanserin group. This difference is highly significant and suggests that ketanserin may have a vascular protective effect in patients with intermittent claudication. This possibility is being investigated in a prospective trial (PACK trial).