Elongating bovine embryos synthesize and secrete interferon-tau (IFNT) beginning 14 d after AI to prevent luteolysis, necessary for pregnancy maintenance. PAGs are synthesized by placental binucleate cells and can be detected in the blood at approximately 25 d after AI. Pregnancy can be detected by measuring ISG15 mRNA (an IFNT-stimulated molecule) in circulating lymphocytes 18 to 22 d after AI or blood PAG 25 d after AI. The objective was to measure ISG15 and PAG during early pregnancy in the same cows and heifers. The hypothesis was that the lymphocyte ISG15 mRNA would be correlated with the circulating PAG. If true, then one explanation is that a larger embryo achieving greater ISG15 would be larger later in pregnancy and synthesize and secrete more PAG. Holstein dairy cows (n = 19 primiparous and n = 23 multiparous) and heifers (n = 18) were AI and blood was collected on d 14, 18, 20, 22, and 25. Total RNA was isolated from blood and the abundance of ISG15 mRNA was quantified using RT-PCR. The same samples were analyzed for plasma PAG concentration using ELISA. The conception rate was 45%. As expected, ISG15 mRNA increased (P < 0.001) in pregnant cows from d 14 (baseline; 0.012 ± 0.007) to d 18 (0.046 ± 0.007), 20 (0.068 ± 0.007), and 22 (0.052 ± 0.007) and was greater (P = 0.014) in heifers compared with cows. There was an increase (P < 0.001) in PAG on d 25 after AI in pregnant cows but no effect of parity. In pregnant cows, PAG concentrations on d 22 were correlated with PAG concentrations on d 25 (r² = 0.58; P < 0.001). PAG concentrations on d 25 were not correlated (P > 0.10) with maximum or mean ISG15 mRNA on d 18 to 22 or ISG15 mRNA on individual days. PAG concentrations on d 22 were modestly correlated with ISG15 on d 20 (r² = 0.20; P = 0.053) and maximum ISG15 mRNA on d 18 to 22 (r² = 0.18; P = 0.066). In summary, the ISG15 signal from d 18 to 22 was not correlated with circulating PAG on d 25. On d 22, correlations with ISG15 mRNA and PAG were modest. We failed to confirm a strong correlation between ISG15 and PAG during early pregnancy in dairy cows and heifers.