Objective - To investigate effects and mechanisms of ergotamine and ergovaline and effects of peramine on reticulum motility of sheep. Sample Population - 3 sheep with indwelling electrodes in the reticulum and samples of reticulum collected from 126 sheep at an abattoir. Procedures - In conscious sheep, motility was recorded as integrated electromyograms from the reticulum. Ergotamine was administered IV alone or in combination with the cholinergic muscarinic receptor antagonist atropine to sheep, and motility of the reticulum was assessed. In vitro, whole wall strips of the reticulum, cut in a direction to record longitudinal muscle activity via force transducers, were placed in 10-mL organ baths and superfused with Tyrode Ringer's solution at 37°C and oxygenated with 95% oxygen and 5% carbon dioxide. Testing involved incubation of reticulum strips with ergotamine, ergovaline, and peramine and measurement of motility of the reticulum tissues. Results - Administration of ergotamine to sheep reduced the frequency of reticulum contractions and increased baseline electromyographic activity (tonus). Frequency was unaffected by atropine, whereas tonus was significantly reduced. In vitro, ergotamine and ergovaline increased tonic contractions and stimulated phasic contractions of reticulum tissues and potentiated electrically stimulated contractions. Atropine and tetrodotoxin reduced tonic contractions, but stimulation of large-amplitude phasic contractions remained. Peramine had no effect on motility of reticulum tissues. Conclusions and Clinical Relevance - Results of the study indicated that peripheral excitatory effects of the ergopeptides on motility of the reticulum appear to be mediated partly through myenteric neurons and muscarinic receptors and also through direct effects on the muscles.