The aim of this study was to assess anti-streptokinase antibody levels in patients treated with intravenous streptokinase for acute myocardial infarction and in patients treated with topical streptokinase for cutaneous wounds. Sixty-two consecutive patients with acute myocardial infarction (age 65±12 years), 42 consecutive patients with streptokinase/streptodornase-treated wounds (age 74±14 years) and a control group of 40 patients with non-streptokinase-treated wounds (age 59±14 years) were studied over a period of 12 months. Blood was taken prior to commencement of treatment and subsequently at intervals of seven days, one month and six months. Serum was analysed for the presence of anti-streptokinase antibodies, using an ELISA technique.Baseline anti-streptokinase levels were similar in all three groups. Over the subsequent six months, the group treated with intravenous streptokinase developed a significant elevation of antibody levels, whereas antibody levels did not rise significantly in the control group. The group treated with topical streptokinase also developed a significant elevation of antibody levels at one month, but the mean level was significantly lower than that in the intravenous group. By six months, anti-streptokinase levels in the topical group had returned toward baseline values.Topical application of streptokinase causes a significant humoral response by one month, which then declines. The response is significantly lower than that caused by intravenous streptokinase. To ensure clinical thrombolytic efficacy, therefore, it may be preferable to avoid intravenous streptokinase in patients who have been treated with topical streptokinase in the preceding six months.