The fast kinetics of binding of sulphonamides to carbonic anhydrase have been examined. Six homologous series of sulphonamides have been studied. In all cases the increase in binding constant in a homologous series is due mainly to an increase in the association rate constant. Meta- and ortho-substituted sulphonamides have lower binding constants also mainly due to a lower association rate constant. The binding of sulphonamides to apocarbonic anhydrase has been measured by a specific affinity method. The effects of homologous series are largely reproduced on the apoenzyme but the effects of positional isomerization are not; the binding process is pH-insensitive. Evidence is presented that the binding process for sulphonamides and carbonic anhydrase involves an intermediate non-coordinate complex which is then converted into the final coordinate complex. Structure-activity relations in the binding of sulphonamides to carbonic anhydrase are examined on the basis of effects on (a) the stability of the intermediate complex; (b) the rate of isomerization into the coordinate complex; (c) the dissociation rate constant.