The relative virulence of isogenic clones of colony type 1 (T1) (piliated) and colony type 4 (T4) (nonpiliated) gonococci was assessed in organ cultures of human fallopian tubes. The rate of damage to fallopian tube mucosa was determined by measurements of ciliary activity and was correlated with the sequential pathologic events observed by light and electron microscopy. During the first 24 hr of the infection, T1 gonococci attached to and damaged the mucosa more rapidly than did T4 gonococci. This damage was manifested primarily by sloughing of ciliated cells. The observation that gonococci attached almost exclusively to nonciliated cells but damaged primarily ciliated cells suggested that this damage was mediated by one or more toxic factors. After attaching, gonococci entered the nonciliated mucosal cells, increased in numbers inside them, and then invaded the subepithelial tissues. Thus, attachment of gonococci to the fallopian tube mucosa may facilitate effective delivery of one or more gonococcal toxins to target cells in the mucosa and may initiate a process by which gonococci traverse the mucosal barrier.