Rats were subjected to chronic hypoxia (10% O2) or hypoxia and hypercapnia (10% O2 + 4% CO2) for 3-4 weeks and their carotid bodies (twenty-three from twenty rats) were compared with those of litter-mate controls. Both chronic exposures, which simulated high altitude or chronic lung disease, caused a 4-10-fold increase in carotid body volume. The larger increases were attributed to higher fixation-perfusion pressures. The organs were fixed by perfusion with glutaraldehyde. Semi-thin (1 micron) sections for light microscopy and ultra-thin sections for electron microscopy were cut at regular intervals and were examined by stereological techniques to determine the nature of the enlargement. The proportion occupied by blood vessels was much increased in both chronic hypoxia and hypoxia plus hypercapnia; the endothelium appeared stretched with conspicuous fenestrations. There were increased numbers of endothelial cells which suggested new growth as well as stretching of endothelium and the mean transectional area of the vessels was increased. The mean surface area of blood vessels per unit area of carotid body was unaltered but the total surface area of blood vessels in the whole carotid body was greatly increased. Both the Type 1 cell nucleus and cytoplasm were increased in size. The proportion nucleus/cytoplasm was unaltered in hypoxia but reduced in hypoxia plus hypercapnia. There were fewer Type 1 cell nuclei per unit area but the estimated total number of Type 1 cell nuclei per carotid body was increased 2-4-fold; this was interpreted as Type 1 cell hyperplasia. Some of the dense-cored vesicles in Type 1 cells were enlarged with eccentric dense cores but their number per unit area of cytoplasm was decreased. Their mean size was not significantly altered. However, the total number of vesicles per carotid body was presumed to be increased because their decreased density in the cell was offset by a greater increase in total Type 1 cell volume. The harmonic and arithmetic mean distances between endothelium and the boundary of glomus tissue were significantly reduced. The harmonic mean distance is an indication of the diffusion distance for gases to and from blood and glomus tissue. The arithmetic mean distance is a measure of the amount of tissue in between. The significance of the vascular enlargement and hyperplasia and the Type 1 cell hyperplasia cannot be assessed at present. We do not know if enlargement is associated with the same, greater, or lesser activity of the organ for a given stimulus.