The calcium channel blockers (CCBs) have been shown to be effective in attenuating the behavioral effects of cocaine in rodents and subjective effects in cocaine-using volunteers. There have been reports indicating that, in the presence of toxic doses of cocaine, the CCBs could actually potentiate cocaine toxicity in rats. The present study was undertaken to make toxicological assessment of the potentiating effect of CCBs in mice. Nifedipine and nimodipine dose-dependently increased the lethalities produced by 80 mg/kg cocaine. In the presence of 40 mg/kg nifedipine, the LD50 of cocaine was decreased from 80.7 to 66.3 mg/kg. Nifedipine potentiated cocaine toxicities in both ICR and Swiss-Webster mice. The increased toxicity was not accompanied by alterations in blood electrolytes. The mechanism of increased cocaine toxicity by CCBs remains to be determined. However, our results corroborate previous findings in rats and suggest that the possibility of an antidote exacerbating the toxic effects of cocaine has to be taken into consideration when screening for therapeutic agents.