Tetracyclines distribute rapidly and extensively in the body, particularly after parenteral administration. They enter almost all tissues and body fluids; high concentrations are found in the kidneys, liver, bile, lungs, spleen, and bone. Lower concentrations are found in serosal fluids, synovia, CSF, ascetic fluid, prostatic fluid, and vitreous humor. The more liquid-soluble tetracyclines (doxycycline and minocycline) readily penetrate tissues such as the blood-brain barrier. They also are present in saliva and tears.

Because tetracyclines tend to chelate calcium ions (less so for doxycycline), they are deposited irreversibly in the growing bones and in dentin and enamel of unerupted teeth of young animals, or even the fetus if transplacental passage occurs.