ABSTRACT: We evaluated liver transcriptome throughout gestation and early lactation of purebred and crossbred beef cows (Angus, Hereford and their F1 crossbreeds, CR), grazing high or low herbage allowances (HA) of native grasslands (4 and 2.5 kg DM/kg BW annual mean; n = 16) using an Agilent 4x44k bovine array. A total of 4,661 transcripts were affected by days (272 M-bM-^IM-% 2.5-fold difference, FDR M-bM-^IM-$ 0.10) and 47 pathways were altered during winter gestation (-165 to -15 days relative to calving, d). Gluconeogenesis and fatty acid oxidation pathways were substantially upregulated, while cell growth, DNA replication and transcription pathways were downregulated (FDR M-bM-^IM-$ 0.25). We observed only small changes in the liver transcriptome during the early lactation period (+15 to +60 d). A total of 225 genes were differentially expressed (47 M-bM-^IM-% 2-fold difference, FDR M-bM-^IM-$ 0.10) between HA. The majority of those were related to glucose and pyruvate metabolism and were upregulated in high HA, reflecting their better metabolic status. Two genes were upregulated in CR cows, but 148 transcripts (74 M-bM-^IM-% 2-fold change difference, FDR M-bM-^IM-$ 0.10) were affected by the HA and cow genotype interaction. The transcriptional changes observed indicates a complex and previously unrecognized adaptive program in beef cow liver. We report novel candidate genes, metabolic pathways, and regulatory mechanisms, which can be used as targets of future studies. Complete randomized block design with two spatial replications and a factorial arrangement of herbage allowance (HA) and cow genotype (CG). Herbage allowance treatments represented 4 and 2.5 kg DM/kg BW of annual mean (HI and LO, respectively). Four purebred (PU M-bM-^@M-^S Hereford, H and Angus, A) and four crossbred (CR - F1, HA and AH) multiparous pregnant cows (5 to 6 year-old), were evaluated per treatment (HI-CR, HI-PU, LO-CR, and LO-PU) throughout the gestation and lactation period (-165 to +60 days relative to parturition, days). Cows belonged to or were descendants of experimental animals generated as part of a diallel crossbreeding experiment carried out for 10 years at the Experimental Station and were assigned to the same forage allowance (HI or LO) since May 2007 and gestated and lactated one calf every year from 2007 to 2009.