The plot concerns a small group of people who are forced to flee from their base (which happens to be a Mission) in an old school bus when the VC launch a vicious assault upon it. Along the way they are joined by a group of three battle hardened American Special Forces soldiers and together they desperately fight to make it to safety.

Jack Kaplan is a US Army Soldier and Weapons Expert liberated by a "rescue team", he returns home to the United States only to find out that his wife Diane has been captured by infatuated gangster Duffy Collins. Kaplan embarks on a mission to find his wife, running into characters like Digger, Man With The Golden Hand, and the treacherous femme fatale Eve. He is a man on a mission.

The titular "Mad Dog", actually goes under the very anonymous name "Nick Nolte", and is played by Romano Kristoff, whom you may or may not remember from such classics as "Warbus", "Double Edge", or "Tough Cops". He is a cop who doesn't take it easy when the mob executes his stripper-sister, and he goes after them to get revenge at all costs. Another Phillipino superstar, Jim Gaines, has a small cameo in "Mad Dog II" as a snitch who gets offed in the bathroom.

After a dangerous top-secret formula is stolen, a government agent traces the thieves back to a mysterious island and a secret-society of Ninjas.

Peter Harris and Major Scott team up together to save the country form a communist uprising.