The concurrent administration of dantrolene and verapamil has the theoretical advantage of being more efficacious than dantrolene alone in the treatment of malignant hyperthermia. However, the combination has been reported to cause fatal hyperkalemia in pigs. The present study evaluated the serum concentrations of cations, serum osmolarity, and cardiovascular responses in 20 mongrel dogs after dantrolene with and without the concurrent administration of verapamil. The dogs were randomly classified into four groups of five dogs each: group 1 received neither dantrolene nor verapamil; group 2 received three successive intravenous doses of dantrolene (1, 3, and 6 mg/kg) at 30-minute intervals; group 3 received verapamil 0.1 mg/kg IV bolus, followed by a continuous infusion of 5 micrograms.kg-1.hr-1; and group 4 received verapamil as in group 3, followed by dantrolene as in group 2. Measurements were made at 15-minute intervals for 2 1/2 hours. Progressive and similar statistically significant increases in mean serum potassium occurred after 105 minutes in dogs given dantrolene (group 2, mean peak serum potassium levels 5.4 +/- 0.5 mmol/L) and after 90 minutes in dogs given verapamil-dantrolene (group 4, 5.2 +/- 1.6 mmol/L). A statistically significant decrease in serum sodium levels was also found in groups 2 and 4. One dog in group 4 developed intermittent second-degree heart block after the final dose of dantrolene. Serum calcium levels (ionized and total) tended to decrease in groups 2 and 4. There were no statistically significant differences in osmolarities, cardiac outputs, or mean arterial blood pressures among groups. In summary, significant elevations of serum potassium were observed in this dog model given dantrolene with and without verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)