The effect of suppressive therapy on the cytology of thyroid nodules and its usefulness in classifying lesions with indeterminate fine needle aspiration (FNA) results were evaluated. The study group consisted of 19 thyroid nodules (6 adenomatoid nodules and 13 neoplasms) aspirated before and while the patients were on suppressive therapy. The control group consisted of nine nonsuppressed nodules (four adenomatoid nodules and five neoplasms) aspirated twice. Both aspirates of each nodule were compared for differences in cytologic features. Differences between aspirates were detected in three suppressed and one nonsuppressed adenomatoid nodule. Suppression revealed no effect on the cytology of thyroid neoplasms and on 50% of adenomatoid nodules. Repeat FNAs allowed correct classification of 3/14 suppressed and 2/2 nonsuppressed nodules with indeterminate diagnoses on initial FNA. Our results indicate that lack of a cytologic response to suppressive therapy does not confirm a neoplastic diagnosis since it can be observed in both neoplastic and nonneoplastic nodules. However, repeat FNA, with or without suppressive therapy, may help to establish the correct diagnosis in difficult cases.