First trimester amniotic fluid is an ultrafiltrate of maternal plasma and constitutes the major component of gestational sac volume (GSV). We hypothesized that GSV, assessed by 3-dimensional (3-D) ultrasound volumetry, would reflect function of the early uteroplacental unit and therefore provide a basis for predicting pregnancy outcome. We tested this hypothesis in 38 pregnancies which had first trimester GSV measurements by two investigators thus allowing determination of interobserver variation. Gestational age (GA) was based on a careful history and conventional 2-dimensional ultrasound measurements. Serum for beta-hCG, estradiol (E2) and progesterone (P) was obtained at the time of ultrasound examinations. "Normal" outcome was defined as confirmation of a viable fetus. "Abnormal outcome" was defined as either a "blighted ovum" or embryonic demise. Statistical analysis was performed by Independent t-test and regression analysis. There were 31 "normal" and 7 "abnormal" pregnancies studied between 5 and 11 weeks gestation (mean +/- SD 8.3 +/- 1.3 weeks). GSV was significantly correlated to GA (r = 0.74, P < 0.001), higher than to beta-hCG (r = 0.40, P = 0.034), E2 (r = 0.70, P < 0.001) and P (r = 0.21, P = 0.334), respectively. In the abnormal group 2/2 pregnancies with a twin sac had a GSV within 1 SD of the mean. 3/5 cases of missed abortions or blighted ovum had a GSV < 2 SD of the mean. The interobserver correlation was high (r = 0.99, P < 0.00f2p4This is the first clinical study investigating the diagnostic use of 3-D ultrasound volumetry in first trimester pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)