This pulse-exposure model (PULSETOX) is based on the simple one-compartment first-order kinetics (1CFOK) equation. It tracks the accumulation of waterborne organic chemicals by fish and predicts acute toxicity by means of previously established relationships between whole-body residues and lethality. The predictive capabilities of the model were tested with a data set of 27 acute pulse-exposure lethality tests with larval fathead minnows (Pimephales promelas) exposed to pentachlorophenol (PCP). Tests included eight single exposures (2 to 96 h) and 19 multiple exposures, which varied in the number (2 to 15) and duration (2 to 24 h) of pulses, and time interval between pulses (6 to 24 h). Experimental work included determination of 1CFOK kinetics parameters from [14C]PCP uptake and clearance, and from time-toxicity curves. Lethality was expected in any exposure regime where the fish reaches or exceeds the critical body residue (CBR) of 0.30 mmol PCP/kg fish (sd, ±0.02; n = 11). Using the CBR endpoint, the model accounted for between 90 and 93% of variability in the observed lethality data, depending on the toxicokinetic parameters employed. Predictive power of the model was optimized by using kinetics parameters derived from the toxicity curve for pulse-toxicity tests as shown by the regression: predicted LC50 = 1.04±(observed LC50) + 0.01 (p < 0.001, r2 = 0.94, n = 27).