Recombinant thyrotropin has been produced by novel methods of transient or stable transfection of alpha and hTSH beta minigenes into Chinese hamster ovary cells. Utilizing products produced in a large scale bioreactor as well as a hollow fiber bioreactor, we have been able to purify several hundred milligrams of this product. In general, the recombinant product is more sialylated than standard pituitary TSH and consists of at least 7 isoforms differing primarily in sialic acid content. The more sialylated forms have less in vitro biologic activity, but a longer metabolic clearance rate and enhanced in vivo biologic activity. Various analogs of TSH have also been produced by modifying various regions of the beta subunit of TSH. Such analogs appear to have different in vitro as well as in vivo biologic activity. The role of specific carbohydrate chains in the action of TSH has been studied by sequential enzymatic deglycosylation of recombinant TSH followed by characterization in in vitro and in vivo bioassays. Through a Cooperative Research and Development Agreement with the Genzyme Corporation (Boston), recombinant human TSH is being used for clinical studies in patients with thyroid cancer. This product is expected to stimulate uptake of radioactive iodine for both diagnostic and therapeutic purposes and to obviate the need for performing uptake studies in hypothyroid patients. An Investigational New Drug Application has been approved by the Food and Drug Administration and phase I and II clinical trials have been completed at NIH and 4 other medical centers showing preliminary efficacy and safety in 19 patients. Phase III trials are currently being planned.