This study was undertaken to evaluate the effects of pretreatment with calcium channel antagonists (nimodipine or verapamil) on the formation of methemoglobin produced by sodium nitrite. Unexpectedly, the pretreatment of animals with control injections of physiological saline 2 hours before the nitrite administration reduced the amount of methemoglobin found in the blood 25 minutes later. When either of the calcium channel antagonists was given 2 hours before the administration of sodium nitrite, the saline effect was eliminated. When the injections of physiological saline or either of the calcium channel blockers were divided 24 hours before the nitrite administration, all reduced the amount of methemoglobin formed relative to rats that received no pretreatment. A tentative hypothesis is that the reduction of the nitrite-induced methemoglobin can be induced by the stress of handling and intraperitoneal injection and that this stress effect can last at least 24 hours. It is likely that whatever stress-related mechanism is involved in reducing methemoglobin levels, this effect can be reduced by the presence of "L channel" voltage-sensitive calcium antagonists or their active metabolites.