OBJECTIVE, DESIGN AND METHODS: Although TRH testing has been eliminated in the diagnosis of most benign thyroid diseases, it is still controversial whether or not it can be replaced by ultrasensitive determination of basal TSH for monitoring optimal TSH suppression in thyroid cancer patients. We compared basal and TRH-stimulated TSH values measured by a 2 nd generation assay (lower detection limit 0.1 mU/l) and by a 3 rd generation assay (lower detection limit 0.005 mU/l) in 209 thyroidectomized thyroid cancer patients under suppressive levothyroxine treatment. RESULTS: In the 2 nd generation assay all patients had basal TSH values < 0.1 mU/l (criterion of admission in the study), and the TRH-stimulated TSH values were above the lower detection limit in 47% of the patients (range < 0.1-1.0 mU/l). In the 3 rd generation assay TSH was above the lower detection limit in 67% under basal conditions (range < 0.005-0.098 mU/l), and in 83% after TRH stimulation (range < 0.005-1.000 mU/l). We observed close correlations (p < 0.001) between basal and TRH-stimulated TSH in the 3 rd generation assay (r = 0.86), between TRH-stimulated TSH in the 2 nd and 3 rd generation assay (r = 0.95), and between TRH-stimulated TSH in the 2 nd generation assay and basal TSH in the 3 rd generation assay (r = 0.73). The ratio between TRH-stimulated and basal TSH values was in the average range 7-9 : 1. Subdividing the patients in three subgroups based on the TRH-stimulated TSH values from the 2 nd generation assay, the corresponding basal TSH values (median and [25.-75. percentile]) from the 3 rd generation assay were < 0.005 [< 0.005-0.010] mU/l in subgroup A (2 nd generation stim. TSH: < 0.15 mU/l), 0.032 [0.021-0.040] mU/l in subgroup B (2 nd generation stim. TSH: 0.15-0.4 mU/l), and 0.066 [0.046-0.085] mU/l in subgroup C (2 nd generation stim. TSH: > or = 0.5 mU/l). CONCLUSIONS: Even in those thyroid cancer patients where a high degree of TSH suppression is the therapeutic goal, 3 rd generation TSH assays enable a reliable adjustment of the levothyroxine dose by basal TSH determinations. In laboratories still using 2 nd generation assays, the monitoring of maximal TSH suppression in patients with high-risk thyroid cancer should be performed by TRH testing.