The rapid onset of cholinergic crisis after intoxication with highly toxic organophosphorus compounds calls for pre-clinical administration of effective antidotes as early as possible. For this purpose, i.m. administration of the antidotes by autoinjectors is desired to allow early treatment also in the absence of a physician. Besides atropine, oximes with broad antidotal spectrum are considered valuable adjuncts that should be included in antidotal mixtures. To circumvent the problem of limited stability of the new-generation oximes, dry/wet autoinjectors were developed in which the unstable solid is dissolved by a diluent in an adjacent chamber upon activation of the device. In this study the tolerance, bioavailability and pharmacokinetics of 500 mg HI 6 [1-(((4-(aminocarbonyl) pyridinio)methoxy) methyl)-2-((hydroxyimino)methyl) pyridinium dichloride monohydrate] or 200 mg HLö 7 [1-(((4-(aminocarbonyl) pyridinio)methoxy)methyl)-2,4- bis((hydroxyimino)methyl)pyridinium dimethanesulfonate] in combination with 2 mg atropine sulfate versus atropine alone, delivered by two dry/wet autoinjector types, were investigated in eight male beagle dogs (16 kg) in a complete cross-over design. The dogs tolerated the six injections with 3-week intervals without any symptoms of discomfort. Nonetheless, CPK activity increased, peaking at 6 h after injection. In contrast to atropine which merely led to a marginal increase, HI 6 plus atropine increased the baseline CPK activity about 10-fold, and HLö 7 plus atropine about 20-fold, regardless of the injector type. The HI 6 autoinjectors from Astra Tech were from an irregular production batch which did not deliver the declared HI 6 dose. The HLö 7 autoinjectors from Astra Tech and both Binaject autoinjectors from STI functioned well: the bioavailability was complete with tmax values of about 25 min as observed after conventional i.m. injection. The absorption half-time was about 8 min, elimination t1/2 about 50 min, and Vapp 0.26 l/kg. The urinary recovery of unchanged oximes was 70-80%, the renal clearance being the same as for inulin. Unexpectedly, hematocrit and hemoglobin content of blood decreased by about 15% within 2 h and reached pre-treatment values after 6-24 h. This decrease was observed with all three drug treatments and could not be accounted for by blood loss (< 4%), thus pointing to an atropine effect. In conclusion, the newly developed dry/wet autoinjectors appear suitable for the administration of atropine and an oxime stored in solid form.