Following ingestion of a beta-carotene isomer mixture (Betatene) containing nearly equal amounts of all-trans and 9-cis beta-carotene (all-trans/9-cis beta-carotene ratio approximately 1.5), concentrations of all-trans beta-carotene increased for 6 or 8 h in the chylomicron fraction of plasma from four of seven human subjects. A substantially lower increase in the 9-cis beta-carotene concentration was observed, with the accumulation of the all-trans isomer being 10- to 50-fold higher than that of the 9-cis isomer, calculated on the basis of the beta-carotene isomer pattern in the ingested mixture. A similar effect was observed in the VLDL fraction. Three of the seven subjects did not respond to beta-carotene ingestion. In the subjects that did respond, the all-trans/9-cis beta-carotene ratios in chylomicrons and VLDL suggest an efficient isomer-selective mechanism for intestinal uptake across the mucosa or very rapid elimination into tissues.