To study the overt toxicosis of intraperitoneally (IP)-administered single doses of cholecalciferol (D3), groups of male CF-1 mice (N = 12) were given graded doses of D3 in corn oil and observed for 21 days. There was a 2- to 4-day onset of signs, including ocular squinting, reluctance to move, lethargy, weakness, anorexia, hunched posture, rough haircoat, and dehydration. This was followed by tremors, coma, and death (large doses) or gradual recovery. Deaths occurred 3 days (larger doses) to 21 days after D3 injection. The linear regression of mortality probits on log10 dose was Y = 7.332X-10.653. The median lethal dose (LD50) of D3 and 95% confidence limits were 135.4 mg/kg (112.2-157.4 mg/kg). To screen potential antidotes against acute D3 toxicosis, groups of mice (N = 12) were given subcutaneous (SC) injections of various substances beginning 2 days after IP injection of a large dose of D3 (300 mg/kg). Substances were given once or twice daily in constant volumes of saline solution (66.8 ml/kg) for 7 days. Two control groups were given D3 but no treatment. They both had 91.7% mortality; their mean (+/- SD) survival time (MST: censored to 21 days observation) was 6.8 +/- 4.7 days and 10.3 +/- 7.0 days. Mortality and MST were not affected significantly (P greater than 0.05) by once-daily injection of saline solution, saline containing dexamethasone (DEX), or saline containing the following substances with or without DEX: ascorbate; citrate; dimercaptosuccinic acid; oxytetracycline; ZnSO4; or MgCl2.(ABSTRACT TRUNCATED AT 250 WORDS)