Cutaneous myiasis in sheep arising from the activity of Lucilia cuprina larvaecan result in significant physiological changes in susceptible animals. The stress imposed on the pituitary-adrenal axis of the sheep in response to myiasis and acute restraint is the subject of this investigation. Merino wethers were exposed to handling restraint, and blood sampling, during examination for blowfly strike; where necessary, they were treated for cutaneous myiasis. Significant changes in the plasma concentrations of immunoreactive β-endorphin (β-EP), ACTH and cortisol were found in sheep with extensive myiasis, as compared with unstruck sheep or those with only localized myiasis. In five susceptible sheep with extensive cutaneous myiasis, mean plasma levels of β-EP, ACTH and cortisol were 307 ± 71 pg ml-1, 953 ± 58 pg ml-1 and 232 ± 46 nmoll-1 respectively, compared with 818 ± 89 pg ml-1, 641 ± 41 pg ml-1 and 107 ± 17 nmol I-1 in six unstruck sheep handled similarly. Whereas significant increases in plasma ACTH and cortisol can result from pituitary-adrenal responses to acute emotional or surgical stress, and are usually accompanied by a concomitant release of β-EP from the pituitary, the present findings indicate a marked reduction in β-EP levels and a significant increase in ACTH and cortisol in sheep following blowfly strike and acute handling restraint. This result suggests that cutaneous myiasisin susceptible sheep can alter the pituitaryadrenal response to acute restraint stress, and this could occur either by an alteration of precursor processing in the pituitary or by the selective release of ACTH.