In July 1990 the new standardized grading scheme for the International Society for Heart and Lung Transplantation was established. One of the purposes of "splitting" the grades was to learn the significance and outcome of the various grades proposed. Between January 1990 and November 1992, 263 grade 1A, 19 grade 1B, and 100 grade 2 "new" rejection episodes were identified at our institution. These episodes occurred in 86 adult recipients who underwent transplantation between January 1990 and August 1992 and 98 recipients who underwent transplantation before January 1990, in whom the episodes occurred more than 1 year from the date of transplantation. The outcome of the episode was determined on subsequent endomyocardial biopsy samples to be resolution or "progression" to a higher grade. The percentage of focal mild (grade 1A) rejection episodes progressing to a moderate (grade 3A) rejection in the first 6 months after transplantation was 24.4% (20 of 82) compared with a progression rate of 5.1% (3 of 59) and 2% (3 of 149) in episodes occurring beyond 6 months and 1 year after transplantation, respectively (p < 0.005). Of the focal moderate (grade 2) rejection episodes receiving no augmentation of immunosuppression, 35.7% (5 of 14) occurring within the initial 6 months and 7.3% (3 of 41) of all such episodes diagnosed beyond 1 year after transplantation progressed to a moderate rejection. A similar trend was seen in the focal moderate rejection episodes that received augmentation of immunosuppression: 26.3% (5 of 19) of episodes occurring within 6 months and 0 of 15 of all episodes occurring beyond 1 year after transplantation progressed to a moderate rejection.(ABSTRACT TRUNCATED AT 250 WORDS)