At a silo outside Rock, Kansas, an oxidizer transfer line carrying NTO ruptured on August 24, 1978. The liquid fuel missiles were prone to developing leaks of their toxic propellants. The fire started when hydraulic fluid used in the Titan II was ignited by a welding torch. In August 1965, 53 construction workers were killed in fire in a missile silo northwest of Searcy, Arkansas. There were several accidents in Titan II silos resulting in loss of life and/or serious injuries. The fuel was Aerozine 50, a 50/50 mix of hydrazine and UDMH, and the oxidizer was NTO. The Titan II's hypergolic fuel and oxidizer ignited on contact, but they were highly toxic and corrosive liquids. The diameter of the second stage was increased to match the first stage. The same first-stage rocket engine was used with some modifications. The RP-1/LOX combination was replaced by a room-temperature fuel whose oxidizer did not require cryogenic storage. The Martin Company was able to improve the design with the Titan II. Several Atlas and Titan I rockets exploded and destroyed their silos, although without loss of life. Liquid oxygen is dangerous to use in an enclosed space, such as a missile silo, and cannot be stored for long periods in the booster oxidizer tank. The main reason was to reduce the cost of maintenance by $72 million per year the conversions were completed in 1981.

The USGS was already in use on the Titan III space launcher when work began in March 1978 to replace the Titan II guidance system. The USGS used a Carousel IV IMU and a Magic 352 computer. When spares for this system became hard to obtain, it was replaced by a more modern guidance system, the Delco Electronics Universal Space Guidance System (USGS). The missile guidance computer (MGC) was the IBM ASC-15. It used an inertial measurement unit made by AC Spark Plug derived from original designs from the Charles Stark Draper Laboratory at MIT. The first Titan II guidance system was built by AC Spark Plug. The Titan II used the LR-87-5 engine, a modified version of the LR-87, that used a hypergolic propellant combination of nitrogen tetroxide (NTO) for its oxidizer and Aerozine 50 (a 50/50 mix of hydrazine and unsymmetrical dimethylhydrazine (UDMH) instead of the liquid oxygen and RP-1 propellant of the Titan I. Most of the Titan rockets were the Titan II ICBM and their civilian derivatives for NASA.

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