OBJECTIVE To test the usefulness of estrogen priming to enhance the growth hormone (GH) response following stimulation with clonidine hydrochloride in short children. METHODS Randomized and patient series. METHODS Pediatric endocrine clinic in a referral center. METHODS Seventy-three children (63% male) between 1.8 and 15.4 years of age (mean age, 8.8 years) with growth problems who underwent clonidine GH stimulation tests were randomly assigned to receive either estrogen pretreatment or no pretreatment. An additional 49 subjects, seen before or after the randomized study and who did not receive conjugated estrogen, are also described. METHODS Consecutive sample. METHODS Estrogen pretreatment consisted of 2.5 mg of conjugated estrogen (Premarin) to be taken the evening before and the morning of the clonidine GH stimulation test. Growth hormone concentrations were determined before and 60 and 90 minutes after the subjects received oral clonidine hydrochloride (5 micrograms/kg) by a laboratory blinded to the subject's estrogen status. Growth hormone concentrations greater than 10 micrograms/L were considered normal. RESULTS Eight of the 73 subjects failed both clonidine and arginine-insulin GH stimulation tests. We analyzed the GH data from the 65 GH-sufficient subjects to determine the effect of estrogen pretreatment on the specificity of the clonidine GH stimulation test. There were no statistically significant differences in the mean GH concentrations between the two groups at any time point during the test. CONCLUSIONS Our data demonstrate that estrogen priming does not improve the diagnostic yield of clonidine GH stimulation tests.