In Paramecium, as previously described, the nuclear mutation cl(1) is incompatible with wild-type mitochondria (M(+)); however, all cl(1)/cl(1)M(+) cells eventually overcome this incompatibility (Sainsard, Claisse and Balmefrezol 1974). We have studied the kinetics and genetic basis of the spontaneous restoration of harmony between nucleus and mitochondria. We also studied the modification of these kinetics following microinjection of compatible mutant mitochondria into cl(1)/cl(1)M(+) cells. We demonstrate that nucleo-mitochondrial readjustment is always achieved by mitochondrial changes that fall into two classes. The first class corresponds to spontaneous mitochondrial mutations affecting the amount of cytochrome aa(3) and is similar to the previously described M(cl) and M(su) mutations (Sainsard-Chanet 1978; Sainsard 1975). The nature of the second class of modification is not yet understood; it may correspond either to a mitochondrial "adaptation" or to an unusual type of mutation arising and reverting at high frequency.