In order to evaluate if the assessment of the paradoxical GH responses to TRH in diabetic subjects could be altered by the presence of spontaneous fluctuations in plasma GH levels, we compared GH responses to TRH and to saline injection in 19 insulin-dependent diabetic patients. We observed significant increments (greater than 5 ng/ml) in plasma GH levels after TRH iv administration in 5 of 19 patients (26%); on the other hand, a significant increase was also observed in 6 patients (31%) after saline. We conclude that, at least in some diabetics, spontaneous GH pulses might be misinterpreted as paradoxical GH responses after a nonspecific stimulus administration. Moreover, the real existence of the paradoxical GH response to TRH has to be assessed using the following strict criteria: a sufficient magnitude in GH increment (greater than 5 ng/ml), the comparison of the kinetics of GH secretion after TRH and saline in the same patient, the presence of a significant GH rise above basal levels within the first 30 min after TRH injection.