Several observations suggest that the course of muscular dystrophy and other myopathies may be sex-influenced. Clinically, muscular dystrophy is less severe in women than in men ( l ) , and the female carrier of the Duchenne gene suffers little muscle impairment though her serum enzymes may be higher than normal ( 2 ) . Experimentally, dystrophic female mice grow better and live longer than do dystrophic male mice ( 3 ) , and steroid-induced myopathy is less severe in the female than the male mouse (4). Finally, the synthetic estrogenic substance, diethylstilbestrol (DIES), appears to be an anabolic agent ( 5 , 6) and has been found in skeletal muscle after administration to dowstic animals (7, 8 ) . These observations and others that will be discussed below suggested that estrogen administration might be useful in DMD. This report summarizes the effects on the serum enzymes and selected muscle parameters in three patients with DMD, treated for 6 months to 3 years with DIES.Methods. The diagnosis of DMD was established in each patient by history, physical and neurological examinations, serum enzyme and lactate dehydrogenase (LDH) isozyme analyses, similar enzyme studies in family members, electromyography, and the histological examination and enzyme assay of several muscle biopsies. T.M., B.C. and D.S. were 13, 11 and 4 years of age, respectively, at the start of their studies, Their muscular disability was quantitated using a 0-10 grade scale (9) (0, normal; 10, totally disabled). T.M.'s disability was grade 6-7; B.C.'s was grade 6-7 ; and D.S.'s was grade 3.Each therapeutic trial consisted of four periods. Period 1 was the control or pretreatment period. Period 2 was the period during which DIES was initially administered. Dur-ing Period 3 DIES was discontinued; and during Period 4 DIES was readministered.The dose of DIES,was 2 to 5 mg/day.During each period, multiple venous blood samples were collected as atraumatically as possible, shortly after arising. Serum was analyzed spectrophotometrically, within 24 hr, for LDH by the method of Cohen and Larson (10) and creatine phosphokinase (CPK) by the method of Rosalki (11). Control serum was analyzed simultaneously, to insure reagent stability. The upper normal limit for LDH is 390 units/ml serum and f o r CPK 50 milli-International Units (mIU) /ml serum.Muscle evaluations were performed at the start of Period 1 and end of each subsequent period by our chief physical therapist. He followed a specific protocol ( 1 2 ) and had no knowledge of the patient's therapy status. These evaluations included manual muscle testing, measurement of limb circumference, joint goniometry, and measurement of the time required to perform certain tasks.Other tests performed at appropriate intervals included complete blood counts; urinalyses; X-ray examination of the chest; radiodensity of the fingers; creatinine clearance and blood urea nitrogen ; electrocardiographic and vectorcardiographic examinations ; electromyography ; serum cholesterol and triglycerides ; glucose tolerance and ...