Summary:The semisynthetic lisuride derivative transdihydrolisuride (terguride, TDHL) is an effective antiparkinsonian drug. In animals, TDHL appears to possess mixed dopamine agonist-antagonist effects, but this may not be the case in man. Single doses of TDHL were given to 21 subjects with parkinsonism. Overall, TDHL 0.25–0.5 mg caused dose-related improvement in parkinsonism for periods of up to 6 h, although 8 of 21 subjects showed no improvement or deterioration with TDHL 0.5–1 mg. In three patients with levodopa-induced psychosis, the addition of TDHL 0.75 mg daily for 5–10 days did not alter the psychotic state. In three subjects with levodopa-induced dyskinesias, the addition of TDHL 0.75 mg daily for 14 days resulted in a slight increase in the severity of involuntary movements. Side-effects of TDHL, sickness and hypotension, were similar to those observed with levodopa. Transdihydrolisuride caused prolonged inhibition of prolactin release, but unlike levodopa did not elevate plasma growth hormone levels. Additionally, TDHL did cause considerable sedation. These results may be due to combined effects of TDHL on nondopamine as well as dopamine neurotransmitter systems, rather than to partial or incomplete dopamine agonist effects.