Novel ergolines were synthesized and screened in spontaneous hypertensive rats (SHR) with the aim of finding a new class of ergot related antihypertensives. Their prolactin inhibitory effect (measured as nidation inhibition in rats), acute toxicity (LD50) and interference with CNS function (Irwin test) were also evaluated as a measure of selectivity and safety. Modification of the C8 side-chain enhanced antihypertensive activity selectively, while the introduction of substituents in other positions of the ergoline skeleton generally yielded unfavourable results, either by decreasing selectivity or by increasing toxicity.