Sex steroids are known to interfere with the parr-smolt transformation of anadromous salmonids, and environmental estrogens such as nonylphenol have recently been implicated in reduced returns of Atlantic salmon in the wild. To determine the endocrine pathways by which estrogenic compounds affect smolt development and seawater tolerance, groups of juvenile Atlantic salmon were injected with one of five doses (0.5, 2, 10, 40 or 150 μg g⁻¹) of branched 4-nonylphenol (NP), 2 μg g⁻¹ of 17β-estradiol (E₂), or vehicle, during the parr-smolt transformation in April, and the treatment was repeated 4, 8, and 11 days after the first injection. Plasma was obtained for biochemical analysis 7 and 14 days after initiation of treatment. After 14 days of treatment, additional fish from each treatment group were exposed to seawater for 24 h to assess salinity tolerance. The E₂ treatment and the highest NP dose resulted in lower salinity tolerance and decreased plasma insulin-like growth factor I (IGF-I) levels, along with elevated levels of plasma vitellogenin and total calcium. Plasma growth hormone levels were elevated at intermediate NP doses only, and not affected by E₂. After 7 days, plasma thyroxine (T₄) levels decreased in a strong, dose-dependent manner in response to nonylphenol, but after 14 days, this suppressive effect of T₄ occurred at the highest NP dose only. Similarly, E₂ decreased plasma T₄ levels at 7, but not 14 days. Plasma 3,3′,5-triodo-l-thyronine was reduced by E₂ and the highest NP dose after 7 and 14 days of treatment. Plasmacortisol levels were not affected by any of the treatments. The results indicate that the parr-smolt transformation and salinity tolerance can be compromised by exposure to estrogenic compounds. Suppression of plasma IGF-I levels is a likely endocrine pathway for the effects of estrogenic compounds on hypo-osmoregulatory capacity, and the detrimental effects of E₂ and NP on thyroid hormone levels are also likely to compromise the normal parr-smolt transformation of Atlantic salmon.