BACKGROUND: The administration of high doses of glucocorticoids can produce significant side effects including skeletal muscle atrophy, weakness and aberrant pharmacology. However, available reports have yielded conflicting results ranging from facilitatory to no change to inhibitory action of glucocoticoids on neuromuscular transmission. Also, the mechanisms for such changes are not known. Therefore, this study investigated the changes in muscle contractility and pharmacology after prednisolone administration in vivo. METHODS: With institutional approval, Sprague-Dawley rats were randomly allocated to 3 treatment groups, namely prednisolone (10 mg/kg daily for 7 days), saline control (equal volume of saline daily for 7 days) and an age-matched food-restriction group which grew at the same rate as the prednisolone group. On day 8 the rats were anesthetized, mechanically ventilated and the twitch response of the tibialis muscle to supramaximal stimulation of the sciatic nerve at 2 Hz for 2 sec every 12 sec, or at 50 or 100 Hz tetanus for 5 sec were monitored. The peak twitch and tetanic tensions were measured and tetanic fade was calculated. The cumulative dose-response curves of d-tubocurarine (d-TC) in the tibialis muscles were determined. The tibialis muscle weight relative to body weight was measured (muscle index), and the tension per unit muscle mass (i.e., specific tension) was calculated. The control and treatment groups were compared by a one way ANOVA test and P>0.05 was regarded as significant. RESULTS: Prednisolone caused a decline in growth rate and the ED50 of dTC relative to saline. Food-restriction caused a decline in growth rate and an increase in muscle index relative to saline, and a decline in tension relative to prednisolone. CONCLUSIONS: These results indicate that prednisolone can alter the sensitivity of skeletal muscles to dTC even without or before changes in neuromuscular contractility become apparent. Therefore, titration of doses of nondepolarizing neuromuscular blocking agents may be indicated in patients receiving glucocorticoid therapy.