Objectives: To evaluate relations of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) with estrogen (E2) and progesterone (Pg) and its role in pathogenesis and severity of pre-eclampsia (PE). Patients & Methods: At 12th week gestational age (GA) constitutional data, systolic and diastolic blood pressures (SBP and DBP), uterine artery pulsatility index (UAPI) and serum NO, ADMA, E2 and Pg levels were determined for primigravida attending the antenatal care unit. During pregnancy, women who developed PE were categorized as early or late and mild or severe according to ACOG Practice Bulletin of PE guidelines. Studied parameters were evaluated statistically as early predictors for development and severity of PE. Results: Ninety pregnant women developed PE; 39 early and 51 late. Only 13 women had severe and 77 women had mild PE. At 12th week GA, UAPI and serum ADMA levels were significantly higher with significantly lower E2 and NO levels in PE women than women free of PE and in early than in late PE. High SBP at time of PE diagnosis showed positive significant correlation with body mass index (BMI) and serum ADMA levels but showed negative significant correlation with serum NO and E2 levels. Serum ADMA levels showed positive significant correlation with BMI, but negative significant correlation with serum E2 levels. High UAPI, serum ADMA and high BMI were significant early predictors for PE development and severity. Conclusion: Disturbed maternal serum ADMA/NO axis and low E2 serum levels may underlie PE development. High BMI and low E2 level may have a role in PE pathogenesis through induction of high serum ADMA levels. High UAPI and serum ADMA at 12th week GA could be used as early predictors of PE especially early-onset and severe PE.