Two gonococcal strains with differing susceptibility to cefotiam and ceftizoxime, as expressed by the minimum inhibitory concentration (MIC), are exposed to continuously changing concentrations of these antibiotics as they are found in plasma and skin cantharidal blister fluid (CBF) after a single intramuscular application of 1 g. Under the conditions of the plasma level profiles, bacterial density is always greatly but not totally reduced, already during the first 1-1.5 h it declines by 99%. The effect is the more marked the quicker and higher the levels increase. In this respect, facing the less favorable CBF level profiles, a 99% reduction of gonococci takes much longer. While the degree of bacterial susceptibility plays no major role as long as the MIC is highly exceeded, as during invasion, it becomes important when the actual levels come more or less close to the MIC. Then the decline of bacterial density can slow down and even the maximum relative reduction can be affected. Under the condition of equivalent in vitro activity, the superior plasma kinetics of cefotiam leads to better antimicrobial activity, an effect no longer found facing similar CBF kinetics. This demonstrates the need for the inclusion of tissue level data, in so far as infection sites other than blood are simulated. The high degree of antigonococcal activity of the drug concentration time curves for plasma and CBF after cefotiam and ceftizoxime (1 g) allow the expected high cure rates in uncomplicated gonorrhoea.