Inducibility or enhancement of fragility at 16q22 by alpha-interferon has been found in a Danish laboratory and in our laboratory. Several other studies were not able to confirm these findings. We present the results of a large study on peripheral blood lymphocytes of 15 selected controls and 146 selected patients treated in vitro by alpha-interferon. In some of our patients parallel studies with distamycin A were performed. Both interferon and distamycin A induced the same fragility, but only in some patients. Both agents were not consistently able to enhance a spontaneously expressed 16q22 fragility. 16q22 is the location of the metallothionein genes, whose transcription is induced by interferon. The induction of the metallothionein gene transcription and the 16q22 fragility, however, do not seem to be directly related. To explain our findings we advance the hypothesis that fragility at 16q22 may be a modification induced by virus(es) with selective tropism for cells which are differently influenced by a pleiotropic action of interferon.