Plasma acetazolamide levels were measured by an enzymatic assay following single 250-mg oral tablet doses to 20 healthy volunteers; five different lots of acetazolamide tablets from a single manufacturer were used in a balanced incomplete block design. From the measured plasma levels, estimates of the bioavailability parameters (area under the plasma concentration versus time curve, time to peak plasma concentration, and peak plasm concentration) were obtained by least-squares digital computer fitting. No significant differences among the tablets were observed (alpha = 0.05) for the analysis of variance of the area under the curve or time to peak parameters. Two tablets, however, provided statistically higher peak plasma concentrations than the other three. Thus, lot-to-lot bioinequivalence of acetazolamide tablets was observed. Some in vitro tests employed showed general trends for correlation with the in vivo data. However, considerable refinement of these technique appears necessary for in vitro prediction of the observed lot-to-lot bioinequivalence.